Meta-Nitration of Arenes Bearing ortho/para Directing Group(s) Using C-H Borylation.

Abstract

Herein, we report the meta-nitration of arenes bearing ortho/para directing group(s) using the iridium-catalyzed C-H borylation reaction followed by a newly developed copper(II)-catalyzed transformation of the crude aryl pinacol boronate esters into the corresponding nitroarenes in a one-pot fashion. This protocol allows the synthesis of meta-nitrated arenes that are tedious to prepare or require multistep synthesis using the existing methods. The reaction tolerates a wide array of ortho/para-directing groups, such as -F, -Cl, -Br, -CH3 , -Et, -iPr -OCH3 , and -OCF3 . It also provides regioselective access to the nitro derivatives of π-electron-deficient heterocycles, such as pyridine and quinoline derivatives. The application of this method is demonstrated in the late-stage modification of complex molecules and also in the gram-scale preparation of an intermediate en route to the FDA-approved drug Nilotinib. Finally, we have shown that the nitro product obtained by this strategy can also be directly converted to the aniline or hindered amine through Baran's amination protocol.